Superman, Supergirl and Krypto see Earth destroyed on the cover of issue 144 (April 1961), but have to wait for the third story in the issue for it to happen.
Siegel, Swan and Kaye open the book with an entertaining twist on a typical Luthor story. Once again he has created a super device to kill Superman. This time it is “weapon x,” which is powered off of Superman’s own expended energy. He gives the plans to a cell mate, about to be released. He is to break Luthor out, but doesn’t.
He uses the machine successfully against Superman. It doesn’t kill him, but it does weaken him significantly. The guy continues his crime spree, using the weapon every time Superman appears.
But Superman had figured out how the weapon was powered, and kept some kryptonite with him to weaken himself, knowing this would be drawn into the weapon’s power source, weakening the weapon itself. Eventually, Superman is able to overpower the man and toss him back into jail, and back to a cell with a very angry Luthor.
Supergirl and Krypto guest in this Siegel and Plastino story.
A failed experiment in the Fortress of Solitude sets off a chain reaction which destroys the Earth. Bummer. Superman, Supergirl and Krypto survive, but are hauled before an intergalactic court for planetary genocide.
They are all found guilty, even Krypto, and have their powers stripped before being sent to a hostile alien world to die in some horrible way.
But, surprise! None of it happened. It was all a red kryptonite hallucination.
Red kryptonite made for a lot of lame deus ex machinas.